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Abstract In this study, we report observations of propagating radial carpet beams (RCBs) through a turbulent atmosphere at ground level with a 120 m path length. RCBs are a class of nondiffracting, accelerating, self-healing, and self-amplifying beams, and generated in the diffraction of a plane wave from amplitude/phase radial gratings having different spoke numbers. Observations were made at different times of the day. The intensity profile of an RCB becomes complicated when the number of grating spokes used to generate the beam is large, and includes high intensity spots, called main intensity spots (MISs), which are symmetrically placed at the central area around the beam axis and whose number is equal to (twice) the number of spokes of the amplitude (phase) grating used to generate the beam. With the aid of a telescope and a CCD camera, successive frames of the intensity pattern of the RCBs having different levels of structural complexity are recorded at the end of the path. For the data recorded at different times of the day, we calculate the variance of displacements of MISs along the radial direction. We observe that displacements of the MISs increase with increasing mean temperature of the air; on the other hand, as the complexity of the beam intensity pattern increases, the displacements of the MISs decrease. In order to compare the resilience of different RCBs and a well-known structured beam against atmospheric turbulence, we investigate deformation of the intensity profiles of a Laguerre–Gaussian (LG) beam having a topological charge 20 and different RCBs at the end of the path. It is shown that under the same turbulence condition, highly complex RCBs are more resilient to the destructive effects of the atmospheric turbulence. In particular, for the RCBs generated with gratings having 30 spokes and more, the number of MISs of the received intensity patterns is changed by less than 1% even when the turbulence strength is high. But for the LG beam, its intensity ring is clearly broken in different places, which makes it impossible to follow its maximum intensity in the radial direction

Purpose: Higher educational institutions, such as universities of applied sciences, have a significant role in promoting progress towards a sustainable future as defined by the United Nations (UN) sustainable development goals (SDGs). This paper aims to identify how the UN SDGs are featured in master's theses set in work-life contexts. Design/methodology/approach: Using a descriptive review and content analysis, this study identified the number of SDGs appearing in 31 master's theses. Sustainable development (SD) and corporate social responsibility were reflected using the approaches and models in the literature. Finland's eight objectives for committing to SD were used to examine the commitments made by the business school of the university of applied sciences to achieve Agenda 2030. Findings: Emphasising the value of higher education for SD, this study found that SDGs three, eight and 12 appeared most frequently in the theses. Sustainable and responsible dimensions reflected several issues concerning both the worlds of business and industry among the firms and organisations investigated by the master's degree students in the business school at the Jyväskylä University of Applied Sciences. Practical implications: This research holds practical and pedagogical value, serving to encourage master's and PhD students to further explore research on SDGs and to shape public policy. Originality/value: Sustainability was looked at in a new way as investigated by the theses. Ways to integrate the SDGs into management degree programmes and conduct research in the fields of business administration, tourism and hospitality management were identified.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Background and objectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

PurposeIn this study, we retrospectively reviewed the use of flow cytometry (FCM) in the diagnosis of inborn errors of immunity (IEIs) at a single center in Algeria. Sharing insights into our practical experience, we present FCM based diagnostic approaches adapted to different clinical scenarios.MethodsBetween May 2017 and February 2024, pediatric and adult patients presenting with clinical features suggestive of immunodeficiency were subjected to FCM evaluation, including lymphocyte subset analysis, detection of specific surface or intracellular proteins, and functional analysis of immune cells.ResultsOver a nearly seven-year period, our laboratory diagnosed a total of 670 patients (372 (55.5%) males and 298 (44.5%) females), distributed into 70 different IEIs belonging to 9 different categories of the International Union of Immunological Societies classification. FCM was used to diagnose and categorize IEI in 514 patients (76.7%). It provided direct diagnostic insights for IEIs such as severe combined immunodeficiency, Omenn syndrome, MHC class II deficiency, familial hemophagocytic lymphohistiocytosis, and CD55 deficiency. For certain IEIs, including hyper-IgE syndrome, STAT1-gain of function, autoimmune lymphoproliferative syndrome, and activated PI3K delta syndrome, FCM offered suggestive evidence, necessitating subsequent genetic testing for confirmation. Protein expression and functional assays played a crucial role in establishing definitive diagnoses for various disorders. To setup such diagnostic assays at high and reproducible quality, high level of expertise is required; in house reference values need to be determined and the parallel testing of healthy controls is highly recommended.ConclusionFlow cytometry has emerged as a highly valuable and cost-effective tool for diagnosing and studying most IEIs, particularly in low-income countries where access to genetic testing can be limited. FCM analysis could provide direct diagnostic insights for most common IEIs, offer clues to the underlying genetic defects, and/or aid in narrowing the list of putative genes to be analyzed.

Suicide continues to be a considerable health risk among adolescents and is the second leading cause of death among adolescents between the ages of 10 and 24. Middle school-aged adolescents may be at a heightened risk for suicide, as middle school can be rife with intrapersonal and interpersonal stressors. One such stressor may be sexual activity and navigating sexual relationships. Past research has shown that parents can play an important role in helping adolescents cope with stressors at this age, but there is no identified research assessing whether parental conversations about sex are associated with suicidality among adolescents. The current study addressed this gap via secondary data analysis using logistic regression with a sample of 3,568 middle school students (mean age = 12.74; SD = 1.08). Results suggest that parental conversations about sex are a significant protective factor against suicidality, but only among adolescents who report having engaged in sexual activity.

Introduction Far less is known about the preceding factors of antipsychotic use among persons with substance-induced psychosis (SIP) and first-episode psychosis (FEP). There is no prevention research on how persons with SIP differ from persons with other psychosis episodes like FEP. Antipsychotic medication is the general essential and necessary element in the treatment of SIP and FEP1. Antipsychotics are used as first-line therapy, commencing with a low dose and titrating upwards2. There are no exciting treatment guidelines for treating Substance-induced psychosis in the long term. (A review of some studies published by the Oxford Journals Schizophrenic Bulletin indicated that drug-induced psychosis lasted longer than a month in individuals between 1 and 15% of the time.3) The aim of the study was to investigate antipsychotic use and associated factors in persons with SIP and compare it with persons with other FEP Objectives 1 To study the antipsychotic use among persons with SIP compared with FEP from 3 years before until three years after their first diagnosis first incident of psychosis) 2.To study associating background factors with antipsychotic use among patients with SIP Methods Incident Swedish SIP cases (n=7320)during 2006-2016 were identified from health care registers and matched 1: with persons with FEP (n=7320) by age, gender, and calendar year of diagnosis. Prevalence of antipsychotic use was assessed as point prevalence every six months, from 3years before until 3years after the first diagnosis. Factors associating with antipsychotic use among SIP were analyzed with multivariable logistic regression, including information on sociodemographic and work-related background, including disability pension and sickness absence, SIP types, and psychiatric diagnoses. Results Among SIP and FEP, the prevalence of antipsychotic use was low before the first diagnosis (3-7% in SIP, 8-16% in FEP), peaked 6 months after the first diagnosis (23% in SIP, 54% in FEP) and stabilized after that. After 3 years of first diagnosis, 19% of persons with SIP and 45% of persons with FEP used antipsychotics. Antipsychotic use one year after diagnosis among SIP was associated with previous substance use disorder, depression, anxiety, and personality disorder diagnoses, being on disability pension or on long-term sickness absence (>90 days), and cannabis- or multi-substance-induced psychosis. Image: Image 2: Conclusions As expected, patients with FEP were using more frequently antipsychotics compared to SIP except for long-acting antipsychotics. Although SIP is considered short-lived, antipsychotic use after an incident SIP episode is relatively common, especially among those with cannabis SIP with the highest prevalence of antipsychotic use. Previous substance use disorder and cannabis SIP were highly associated with patients who use antipsychotics frequently. Disclosure of Interest None Declared

BackgroundMajor depressive disorder (MDD) exhibits gender disparities, and emerging evidence suggests the involvement of the gut microbiome, necessitating exploration of sex-specific differences.MethodsA review was conducted, encompassing a thorough examination of relevant studies available in Medline via Ovid, Embase via OvidSP, CINAHL, and PsycINFO databases from their inception to June 2023. The search strategy employed specific keywords and Medical Subject Headings (MeSH) terms tailored to major depressive disorder in women, encompassing unipolar depression, depressive symptoms, and dysbiosis.ResultsFive studies were included. Among the four studies, alterations in alpha (n=1) and beta diversity (n=3) in the gut microbiome of individuals with MDD were revealed compared to controls. Gender-specific differences were observed in four studies, demonstrating the abundance of specific bacterial taxa and highlighting potential sex-specific implications in MDD pathophysiology. Correlation analyses (n=4) indicated associations between certain bacterial taxa and the severity of depressive symptoms, with varying patterns between males and females. Studies (n=3) also highlighted promising findings regarding the potential utility of microbial markers in diagnosing MDD, emphasizing the crucial role of sex stratification in understanding the disease pathophysiology.ConclusionsThe findings underscore the importance of recognizing gender-specific differences in the composition of the gut microbiome and its relationship with MDD. Further comprehensive robust studies are required to unravel the intricate mechanisms underlying these disparities.

Intracranial aneurysms (IAs) are rare vascular lesions that are more frequently found in women. The pathophysiology behind the formation and growth of IAs is complex. Hence, to date, no single pharmacological option exists to treat them. Animal models, especially mouse models, represent a valuable tool to explore such complex scientific questions. Genetic modification in a mouse model of IAs, including deletion or overexpression of a particular gene, provides an excellent means for examining basic mechanisms behind disease pathophysiology and developing novel pharmacological approaches. All existing animal models need some pharmacological treatments, surgical interventions, or both to develop IAs, which is different from the spontaneous and natural development of aneurysms under the influence of the classical risk factors. The benefit of such animal models is the development of IAs in a limited time. However, clinical translation of the results is often challenging because of the artificial course of IA development and growth. Here, we summarize the continuous improvement in mouse models of IAs. Moreover, we discuss the pros and cons of existing mouse models of IAs and highlight the main translational roadblocks and how to improve them to increase the success of translational IA research.

BACKGROUND: Pediatric endogenous Cushing syndrome (eCs) is mainly caused by pituitary corticotropin-producing adenomas, and most glucocorticoid-dependent effects progressively regress upon tumor removal. eCs reproduces long-term, high-dose glucocorticoid therapy, representing a clean, natural, and unbiased model in which to study glucocorticoid bona fide effects on immunity. OBJECTIVE: We performed extensive immunologic studies in otherwise healthy pediatric patients with eCs before and 6 to 13 months after tumor resection, as well as in in vitro glucocorticoid-treated control cells. METHODS: Flow cytometry, immunoblotting, enzyme-linked immunosorbent assay, real-time quantitative PCR, and RNA-Seq techniques were used to characterize patients and in vitro glucocorticoid treated cells. RESULTS: Reduced thymic output, decreased naive T cells, diminished proliferation, and increased T-cell apoptosis were detected before surgery; all these defects eventually normalized after tumor removal in patients. In vitro studies also showed increased T-cell apoptosis, with correspondingly diminished NF-κB signaling and IL-21 levels. In this setting, IL-21 addition upregulated antiapoptotic BCL2 expression and rescued T-cell apoptosis in a PI3K pathway-dependent manner. Similar and reproducible findings were confirmed in eCs patient cells as well. CONCLUSIONS: We identified decreased thymic output and lymphocyte proliferation, together with increased apoptosis, as the underlying causes to T-cell lymphopenia in eCs patients. IL-21 was decreased in both natural and in vitro long-term, high-dose glucocorticoid environments, and in vitro addition of IL-21 counteracted the proapoptotic effects of glucocorticoid therapy. Thus, our results suggest that administration of IL-21 in patients receiving long-term, high-dose glucocorticoid therapy may contribute to ameliorate lymphopenia and the complications associated to it.

Abstract We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)−6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.

Gradual solar energetic particle (SEP) events are associated with shocks driven by coronal mass ejections (CMEs). The merging of two CMEs (so-called cannibalistic CMEs) and the interaction of their associated shocks has been linked to some of the most powerful solar storms ever recorded. Multiple studies have focused on the observational aspects of these SEP events, yet only a handful have focused on modeling similar CME–CME interactions in the heliosphere using advanced magnetohydrodynamic (MHD) models. This work presents, to our knowledge, the first modeling results of a fully time-dependent 3D simulation that captures both the interaction of two CMEs and its effect on the acceleration and transport of SEPs. This is achieved by using an MHD model for the solar wind and CME propagation together with an integrated SEP model. We perform different simulations and compare the behavior of the energetic protons in three different solar wind environments, where a combination of two SEP-accelerating CMEs are modeled. We find that particle acceleration is significantly affected by the presence of both CMEs in the simulation. Initially, less efficient acceleration results in lower-energy particles. However, as the CMEs converge and their shocks eventually merge, particle acceleration is significantly enhanced through multiple acceleration processes between CME-driven shocks, resulting in higher particle intensities and energy levels.

IntroductionMulibrey nanism (MUL) is a rare disorder caused by TRIM37 gene variants characterized by growth failure, dysmorphic features, congestive heart failure (CHF), and an increased risk of Wilms’ tumor. Although immune system impairment has been documented in MUL, the underlying mechanisms remain poorly understood.MethodsWe present a case of MUL with progressive lymphopenia and review similar cases from the literature.ResultsOur patient presented with prenatal onset growth restriction, characteristic dysmorphic features, and Wilms’ tumor. She developed progressive lymphopenia starting at 10 years of age, leading to the initiation of intravenous immunoglobulin (IVIG) replacement therapy and infection prophylaxis. Genetic analysis detected a likely pathogenic variant on the maternal allele and copy number loss on the paternal allele in TRIM37. Subsequently a cardiac magnetic resonance imaging was conducted revealing signs of pericardial constriction raising concerns for intestinal lymphatic losses. The cessation of IVIG therapy did not coincide with any increase in the rate of infections. The patient exhibited a distinct immunological profile, characterized by hypogammaglobulinemia, impaired antibody responses, and skewed T-cell subsets with an altered CD4+/CD8+ ratio, consistent with previous reports. Normal thymocyte development assessed by artificial thymic organoid platform ruled out an early hematopoietic intrinsic defect of T-cell development.DiscussionThe immunological profile of MUL patients reported so far shares similarities with that described in protein-losing enteropathy secondary to CHF in Fontan circulation and primary intestinal lymphangiectasia. These similarities include hypogammaglobulinemia, significant T-cell deficiency with decreased CD4+ and CD8+ counts, altered CD4+/CD8+ ratios, and significantly modified CD4+ and CD8+ T-cell phenotypes toward effector and terminal differentiated T cells, accompanied by a loss of naïve CD45RA+ T lymphocytes. In MUL, CHF is a cardinal feature, occurring in a significant proportion of patients and influencing prognosis. Signs of CHF or constrictive pericarditis have been evident in the case reported here and in all cases of MUL with documented immune dysfunction reported so far. These observations raise intriguing connections between these conditions. However, further investigation is warranted to in-depth define the immunological defect, providing valuable insights into the pathophysiology and treatment strategies for this condition.

This paper utilizes concept mapping as a tool for conscious and deliberate knowledge building in mathematics and its extension to algorithms. Currently, alleged defects in mathematics education are obvious: instead of conceptual elaboration, everyday praxis relies on routine computations that are likely to lead into alienated concepts with weak connections to prior knowledge. A concept map visualizes the existing conceptual structure, and whenever new information is brought in, it will be placed in the map by clearly explicating its linkage to the previous concepts. In the Finnish mathematics education, such new knowledge is programming content that is integrated into elementary school mathematics in 2014 Finnish National Curriculum. This content is crystallized as the requirements of computational and algorithmic thinking, the utilization of respective data structures, and adequate amount of hands-on practice to internalize good coding conventions. This study examines secondary (N = 19) and higher education students (N = 10) and their conceptual knowledge of mathematics concentrating on the domain of algorithms in particular. The concept maps drawn by the students are evaluated using the SOLO taxonomy. To conclude, a consensus map of algorithms is represented and linked to the elementary mathematics syllabus.

A thermal lensing approach based on parabolic approximation and Mach-Zehnder interferometer for measuring optical absorption and thermal diffusivity coefficients in pure solvents is described in this work. The approach combines the sensitivity of both thermal lensing methods and interferometry techniques. The photothermal effect is induced by a pump laser beam generating localized changes in the refractive index of the sample, which are observed as a shift in phase of the interference pattern. Each interference pattern is recorded by means of a digital camera and stored as digital images as a function of time. The images are then numerically processed to calculate the phase shifting map for a specific time. From each phase shifting map, the experimental phase difference as a function of time is calculated giving a phase-time transient, which is fitted to a mathematical model to estimate the optical absorption and thermal diffusivity of the sample. The experimental results show that the sensitivity is approximately λ/4800 for the minimum phase difference measured.

Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.

Infections are among the most serious complications in patients with systemic lupus erythematosus (SLE), with bacterial and viral infections being the most common. Non-tuberculous mycobacterial (NTM) infections are quite rare and are typically seen in older patients with SLE with longstanding disease duration treated with corticosteroids. Here, we describe a 39-year-old woman with SLE and an unusual pattern of recurrent NTM disseminated infections. After excluding the presence of autoantibodies against interferon-γ, whole exome sequencing revealed a homozygous polymorphism in the NF-kappa-B essential modulator (NEMO) gene. Primary immunodeficiencies should be included in the differential diagnosis of patients with recurrent opportunistic infections, even in those with iatrogenic immunosuppression.

Abstract While room temperature bulk mercury is liquid, it is solid in its nano-configuration (Ønano-Hg ≤ 2.5 nm). Conjugating the nano-scale size effect and the Laplace driven surface excess pressure, Hg nanoparticles of Ønano-Hg ≤ 2.4 nm embedded in a 2-D turbostratic Boron Nitride (BN) host matrix exhibited a net crystallization at room temperature via the experimentally observed (101) and (003) diffraction Bragg peaks of the solid Hg rhombohedral α-phase. The observed crystallization is correlated to a surface atomic ordering of 7 to 8 reticular atomic plans of the rhombohedral α-phase. Such a novelty of size effect on phase transition phenomena in Hg is conjugated to a potential Hg waste storage technology. Considering the vapor pressure of bulk Hg, Room Temperature (RT) Solid nano-Hg confinement could represent a potential green approach of Hg waste storage derived from modern halogen efficient light technology.

Background: Because of the social and systemic barriers encountered by first-generation college students, this population is at risk for poorer health outcomes. However, there is no identified research investigating whether this includes sexually transmitted infections (STIs). The aim of the study was to identify whether first-generation students were more likely than non-first-generation students to report a history of STIs. Methods: Participants (n = 634) were undergraduate university students at a public institution in the Southeast United States. Using secondary data analysis, this study assessed the relationship between first-generation student status and reported a history of STIs. Participants completed a Qualtrics survey including demographics, first-generation student status, and history of STI(s). Results: First-generation college students are over twice as likely as non-first-generation college students to report a history of STIs after controlling for relevant background variables. Discussion: First-generation college students represent a population that colleges, universities, and high schools can prioritize for STI education, prevention, and testing.

Missing data are unavoidable in the real-world application of unsupervised machine learning, and their nonoptimal processing may decrease the quality of data-driven models. Imputation is a common remedy for missing values, but directly estimating expected distances have also emerged. Because treatment of missing values is rarely considered in clustering related tasks and distance metrics have a central role both in clustering and cluster validation, we developed a new toolbox that provides a wide range of algorithms for data preprocessing, distance estimation, clustering, and cluster validation in the presence of missing values. All these are core elements in any comprehensive cluster analysis methodology. We describe the methodological background of the implemented algorithms and present multiple illustrations of their use. The experiments include validating distance estimation methods against selected reference methods and demonstrating the performance of internal cluster validation indices. The experimental results demonstrate the general usability of the toolbox for the straightforward realization of alternate data processing pipelines. Source code, data sets, results, and example macros are available on GitHub. https://github.com/markoniem/nanclustering_toolbox

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan–stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1–derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

To provide insights into the challenging problem of turbulent convection, Jack Herring used a greatly truncated version of the complete Boussinesq equations containing only one horizontal wavenumber. In light of later observations of a robust large-scale circulation sweeping through convecting enclosures at high Rayleigh numbers, it is perhaps not an implausible point of view from which to reexamine high-Rayleigh-number data. Here we compare past experimental data on convective heat transport at high Rayleigh numbers with predictions from Herring’s model and, in fact, find excellent agreement. The model has only one unknown parameter compared to the two free parameters present in the lowest-order least-squares power-law fit. We discuss why the underlying simplistic physical picture, meant to work at Rayleigh numbers slightly past the critical value of a few thousand, is consistent with the data when the single free parameter in it is revised, over some eleven decades of the Rayleigh number—stretching from about a million to about 1017.

Deaths of despair (DOD) is a new term appearing in public health literature to describe deaths attributable to suicide, liver disease, and drug overdose. In Florida, suicide and liver disease are the 8th and 10th leading causes of death, respectively. Additional mortality data show that the rate of drug overdose deaths in Florida is 12.5% higher than the suicide death rate. Some have hypothesized that economic social determinants of health (SDH) may be responsible for the recent increase in DOD. The current study, using secondary data, sought to identify what county-level SDH were significantly associated with county-level DOD. Using backward regression methodology, the results of the analysis indicate that 44% of the variance in county-level DOD is significantly associated with six county-level SDH: (a) Recent Medical Checkup, (b) Income, (c) Education Level, (d) Age, (e) Mental Health Professionals, and (f) the Income × Age interaction term. Higher than average income, age, and mental health professionals in a Florida county was associated with significantly higher rates of DOD. Higher than average levels of education and recent checkups in a Florida county were associated with a significant decrease in DOD. Possible explanations and implications are discussed.

Despite the counseling field adopting holistic health and developmental frameworks, sexual health is often absent or underrepresented in these discussions. Via content analysis, the authors examined publications in three counseling journals to assess the current state of the sexuality literature in the field. Almost half (46.6%) of publications are on the topic of sexual identity. There are notable gaps in the literature on topics related to anatomy/physiology, sexual functioning, and pleasure/sexual lifestyle. Implications for counselors and counselor training are discussed.

Chagas disease, which manifests as cardiomyopathy and severe gastrointestinal dysfunction, is caused by Trypanosoma cruzi, a vector-borne parasite. In California, the vector Triatoma protracta frequently colonizes woodrat (Neotoma spp.) lodges, but may also invade nearby residences, feeding upon humans and creating the dual risk of bite-induced anaphylaxis and T. cruzi transmission. Our research aimed to assess T. cruzi presence in woodrats in a previously unstudied northern California area, statistically evaluate woodrat microhabitat use with respect to vegetation parameters, and provide guidance for habitat modifications to mitigate public health risks associated with Tr. protracta exposure. Blood samples from big-eared woodrats (N. macrotis) trapped on rural private properties yielded a T. cruzi prevalence of 14.3%. Microhabitat analyses suggest that modifying vegetation to reduce understory density within a 40 meter radius of human residences might minimize woodrat lodge construction within this buffer area, potentially decreasing human exposure to Tr. protracta.